Trypanosomes and leishmanias are parasitic protozoa causing African sleeping sickness (Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense), Chagas' disease (Trypanosoma cruzi), Nagana cattle disease (Trypanosoma congolense and Trypanosoma brucei brucei), Espundia (Leishmania brasiliensis), Kala-azar (Leishmania donovani), and Oriental sore (Leishmania tropica). All of these parasites have a unique thiol metabolism dependant on the flavoenzyme trypanothione reductase, which maintains bisglutathionylspermidine (trypanothione) and monoglutathionylspermidine in the reduced state. This thiol system replaces the glutathione/glutathione reductase (GR) system occurring in their mammalian hosts and is widely accepted as a target for the development of novel therapies to treat trypanosomiasis and leishmaniasis.

Human African trypanosomiasis is invariably fatal if untreated. Current therapy of the late-stage encephalitic disease with the melaminophenyl arsenical drug melarsoprol has unacceptable side-effects with an overall mortality of more than 5% due to the drug itself. Melarsoprol acting as a bis-alkylating agent of dithiols including trypanothione and trypanothione reductase is actively taken up via adenosine transporters of the parasite which recognize the melamine motif. In the recent years appearance of highly resistant parasites to melarsoprol and pentamidine has become alarming and is responsible for the increasing failure rate (under 7%) of melarsoprol after treatment of late stage case of human African trypanosomiasis (HAT), even though the drug has been used for such treatment over the past 50 years. This observation, the first documented in a HAT focus, is dramatic, particularly since no second line trypanocidal drug is actually available for the treatment of the late stage of HAT.
Eflornithine (=DFMO) is effective against both stages of T. b. gambiense infection but not against T. b. rhodesiense. Although the most recent and effective drug against sleeping sickness it is not widely available, difficult to administer and costly for use under African health care conditions. For this reason, in 1995, Aventis limited its production because erflornithine was not enough a profitable drug.
Thus there is a need for compounds which are less costly, less toxic, which induce less resistance and which are able to cross the blood brain barrier in the late stage of the disease.